Buccal and sublingual lyophilised naloxone for opioid overdose reversal: A Phase 1 open-label, random-sequence crossover pharmacokinetic study protocol in healthy volunteers (NalBuc)
4 affiliations
- 1National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
- 2South London and Maudsley NHS Foundation Trust, London, United Kingdom
- 3Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
- 4King’s Clinical Trials Unit, King’s College London, London, United Kingdom
Abstract
Background: Opioid overdose remains a major global public health emergency, with naloxone being an essential response. Benefit from existing naloxone formulations is limited by barriers to acceptability, fixed dosing, and poor real-world carriage. This study describes the protocol for a Phase 1 exploratory investigation of a novel ultra-portable lyophilised naloxone wafer designed to facilitate constant carriage and enable rapid mucosal absorption. Methods: This open-label, randomised, random-sequence, five-way crossover pharmacokinetic (PK) exploratory study will recruit 12–15 healthy adults at a UK clinical research facility. Participants will receive five treatments, each separated by ≥36 hours: buccal naloxone wafer 2 mg, buccal wafer 4 mg, sublingual wafer 2 mg, intramuscular naloxone 0.4 mg, and intranasal naloxone 1.8 mg (Nyxoid®). Blood samples will be collected up to 240 minutes post-dose for PK analysis via validated LC-MS/MS methods. The primary endpoint is time to maximum plasma concentration (Tmax). Secondary endpoints include Maximum Plasma Concentration (Cmax), Time to 50% of maximum concentration (T50%), Area Under the Curve from time zero to 15 minutes (AUC0–15), Area Under the Curve from time zero to infinity (AUCinf), and safety/tolerability. Dose-proportionality and buccal–sublingual comparisons will be explored. Trial Registration:REC: 25/LO/0701; MHRA CTA (IRAS): 1011060. ISRCTN67173532. Results & Significance: This study will characterise the absorption profile, early exposure, and relative bioavailability of a novel naloxone wafer formulated for rapid buccal and sublingual administration. Findings will inform whether this technology could provide a practical, effective alternative to current injectable and intranasal products, with potential to substantially improve naloxone carriage and timely overdose response, and will guide the design of a subsequent, larger confirmatory study.
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BibTeX
@article{utrilla2026buccal,
title = {{Buccal and sublingual lyophilised naloxone for opioid overdose reversal: A Phase 1 open-label, random-sequence crossover pharmacokinetic study protocol in healthy volunteers (NalBuc)}},
author = {Mariana Gonzalez Utrilla and Alexander Baker and Edward Chesney and Kim Lee and Richard Emsley and John Strang},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0347370},
url = {https://doi.org/10.1371/journal.pone.0347370},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Buccal and sublingual lyophilised naloxone for opioid overdose reversal: A Phase 1 open-label, random-sequence crossover pharmacokinetic study protocol in healthy volunteers (NalBuc)
AU - Mariana Gonzalez Utrilla
AU - Alexander Baker
AU - Edward Chesney
AU - Kim Lee
AU - Richard Emsley
AU - John Strang
PY - 2026
DA - 2026/10/27
JO - PLOS One
DO - 10.1371/journal.pone.0347370
UR - https://doi.org/10.1371/journal.pone.0347370
AB - Background: Opioid overdose remains a major global public health emergency, with naloxone being an essential response. Benefit from existing naloxone formulations is limited by barriers to acceptability, fixed dosing, and poor real-world carriage. This study describes the protocol for a Phase 1 exploratory investigation of a novel ultra-portable lyophilised naloxone wafer designed to facilitate constant carriage and enable rapid mucosal absorption. Methods: This open-label, randomised, random-sequence, five-way crossover pharmacokinetic (PK) exploratory study will recruit 12–15 healthy adults at a UK clinical research facility. Participants will receive five treatments, each separated by ≥36 hours: buccal naloxone wafer 2 mg, buccal wafer 4 mg, sublingual wafer 2 mg, intramuscular naloxone 0.4 mg, and intranasal naloxone 1.8 mg (Nyxoid®). Blood samples will be collected up to 240 minutes post-dose for PK analysis via validated LC-MS/MS methods. The primary endpoint is time to maximum plasma concentration (Tmax). Secondary endpoints include Maximum Plasma Concentration (Cmax), Time to 50% of maximum concentration (T50%), Area Under the Curve from time zero to 15 minutes (AUC0–15), Area Under the Curve from time zero to infinity (AUCinf), and safety/tolerability. Dose-proportionality and buccal–sublingual comparisons will be explored. Trial Registration:REC: 25/LO/0701; MHRA CTA (IRAS): 1011060. ISRCTN67173532. Results & Significance: This study will characterise the absorption profile, early exposure, and relative bioavailability of a novel naloxone wafer formulated for rapid buccal and sublingual administration. Findings will inform whether this technology could provide a practical, effective alternative to current injectable and intranasal products, with potential to substantially improve naloxone carriage and timely overdose response, and will guide the design of a subsequent, larger confirmatory study.
SN - 1932-6203
ER -